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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 341 (1990), S. 225-231 
    ISSN: 1432-1912
    Keywords: Adenosine ; Adenosine A1-receptors ; Desensitization ; Locus coeruleus neurones ; Firing rate ; Membrane potential
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Intracellular recordings were performed in α1-pontine slice preparation of the rat brain containing the locus coeruleus (LC). Adenosine (100, 300 μmol/l) and its structural analogues, namely (−)-N6-(R-phenyliso-propyl)-adenosine (R-PIA; 3 – 30 μmol/l) and S-PIA (10, 30 μmol/l), as well as 5′-N-ethylcarboxamido-adenosine (NECA; 3–30 μmol/l) inhibited the firing rate of spontaneous action potentials and produced hyperpolarization; their rank order of potency was RPIA - NECA 〉 S-PIA 〉 adenosine. When applied by superfusion, all agonists strongly desensitized the LC cells; the hyperpolarization never surmounted 6 mV. Upon pressure ejection of adenosine 10 mmol/l from α1- micropipette positioned close to an LC neurone, the membrane potential was raised by 14 mV and the apparent input resistance decreased by 20%. When the membrane potential was hyperpolarized by current injection to α1- similar extent as adenosine did, the fall in input resistance was only 7%. The adenosine uptake inhibitor S-(p-nitrobenzyl)-6-thioguanosine (NBTG) 30 μmol/l decreased the frequency of action potentials alone; on simultaneous bath-application with adenosine 300 μmol/l it potentiated the hyperpolarization caused by the purine derivative. 8-Cyclopentyl-1,3-dipropylxanthine (CPDPX) 0.1 μmol/l had no effect on its own, but it antagonized both R-PIA 30 μmol/l and NBTG 30 μmol/l. A higher concentration of CPDPX (1 μmol/l) facilitated the spontaneous firing. In conclusion, both exogenous and endogenous adenosine activates somatic and/or dendritic A1-receptors of LC neurones leading to an enhancement of potassium conductance and thereby to α1- decreased firing rate and α1- hyperpolarization.
    Type of Medium: Electronic Resource
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